Many secreted proteins, for example, cytokines and cytokine receptors, play a vital role in the regulation of cell growth, cell differentiation, and a variety of specific cellular responses. A number of medically useful proteins, including erythropoietin, granulocyte-macrophage colony stimulating factor, human growth hormone, and various interleukins, are secreted proteins. Thus, an important goal in the design and development of new therapies is the identification and characterization of secreted and transmembrane proteins and the genes which encode them.
Many secreted proteins are receptors which bind a ligand and transduce an intracellular signal, leading to a variety of cellular responses. Other secreted proteins are extracellular proteins that act as ligands by binding a receptor which leads to transduction of intracellular signals and ultimately results in downstream cellular responses. The identification and characterization of receptors and/or ligands permits identification of other molecules and of the signal transduction pathways associated with the receptors and/or ligands, permitting one to identify or design modulators of activity, e.g., receptor agonists or antagonists, modulators of signal transduction, and modulators of downstream cellular responses.
Virtually all cell types respond to extracellular and intercellular cues and induce one or more signal transduction pathways. Among such cell types are cells involved in the development, differentiation, activation, function, and maintenance of hematopoietic cells. These cell types include ones (e.g., B cells and T cells, and subpopulations thereof, such as T helper (TH) cells, including TH1 and TH2 cells) involved in a variety of immune and autoimmune responses, such as inflammatory responses. These responses can contribute to such diverse disorders as pulmonary disorders such as asthma and emphysema, arthritis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, multiple sclerosis, graft-versus-host disease and tissue rejection. As such, identification of secreted proteins involved in some aspect of these cell types is particularly desirable.